Inta Ioana, Vogt Miriam A, Vogel Anne S, Bettendorf Markus, Gass Peter, Inta Dragos
Division of Pediatric Endocrinology, University Children's Hospital Heidelberg, Heidelberg, Germany.
Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute for Mental Health Mannheim, University of Heidelberg, Heidelberg, Germany.
Eur Arch Psychiatry Clin Neurosci. 2016 Oct;266(7):673-7. doi: 10.1007/s00406-015-0649-2. Epub 2015 Oct 19.
NMDA receptor (NMDAR) antagonists induce in perinatal rodent cortical apoptosis and protracted schizophrenia-like alterations ameliorated by antipsychotic treatment. The broad-spectrum antibiotic minocycline elicits antipsychotic and neuroprotective effects. Here we tested, if minocycline protects also against apoptosis triggered by the NMDAR antagonist MK-801 at postnatal day 7. Surprisingly, minocycline induced widespread cortical apoptosis and exacerbated MK-801-triggered cell death. In some areas such as the subiculum, the pro-apoptotic effect of minocycline was even more pronounced than that elicited by MK-801. These data reveal among antipsychotics unique pro-apoptotic properties of minocycline, raising concerns regarding consequences for brain development and the use in children.
N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂可诱导围产期啮齿动物皮质细胞凋亡，并导致长期的精神分裂症样改变，而抗精神病药物治疗可改善这些改变。广谱抗生素米诺环素具有抗精神病和神经保护作用。在此，我们测试了米诺环素是否也能保护出生后第7天的小鼠免受NMDAR拮抗剂MK-801引发的细胞凋亡。令人惊讶的是，米诺环素诱导了广泛的皮质细胞凋亡，并加剧了MK-801引发的细胞死亡。在某些区域，如海马下托，米诺环素的促凋亡作用甚至比MK-801更明显。这些数据揭示了米诺环素在抗精神病药物中具有独特的促凋亡特性，这引发了人们对其对脑发育的影响以及在儿童中使用的担忧。
